We recently developed the Mother Enrichment Program (MEP), a genetic program to facilitate replicative aging studies in yeast [16]. The MEP provides an efficient and inducible selection against newborn daughter cells. When the MEP is active, mother cells continue to divide and age normally, while the division of newborn daughter cells is arrested. The MEP provides the opportunity to follow a cohort of mother cells in liquid culture throughout their entire RLS without any requirement for removing progeny cells. Once cells have reached a desired age, the MEP can be switched off and aged mothers will resume production of viable daughters, allowing for colony-based phenotypic analysis. Compared to pedigree analysis, which is done by single-cell micromanipulation, the MEP can dramatically improve the sensitivity of the LOH assay by increasing the sample number of aged cells by over three orders of magnitude. Here we report our finding that replicative age is accompanied by a progressive decline in rDNA array stability, leading to higher incidence of LOH affecting the right arm of chromosome XII.
